Impact of the COVID-19 Pandemic on Parkinson's Disease and Movement Disorders - SNO Italia
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
VIEWPOINT
Impact of the COVID-19 Pandemic on Parkinson’s Disease and
Movement Disorders
Stella M. Papa, MD,1* Patrik Brundin, MD, PhD,2 Victor S.C. Fung, PhD, FRACP,3 Un Jung Kang, MD,4
David J. Burn, MD, FMedSci,5 Carlo Colosimo, MD, FEAN,6 Han-Lin Chiang, MD,7 Roy N. Alcalay, MD, MS,8 and
Claudia Trenkwalder, MD,9 and the MDS-Scientific Issues Committee
1
Yerkes National Primate Research Center, Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
2
Van Andel Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA
3
Movement Disorders Unit, Department of Neurology, Westmead Hospital and Sydney Medical School, University of Sydney, Sydney,
NSW, Australia
4
Department of Neurology, New York University Grossman School of Medicine, New York, New York, USA
5
Department of Medical Sciences, Newcastle University Medical School, Newcastle, United Kingdom
6
Department of Neurology, Santa Maria University Hospital, Terni, Italy
7
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
8
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
9
Paracelsus-Elena Klinik, Kassel, Department of Neurosurgery, University Medical Center, Goettingen, Goettingen, Germany
The COVID-19 Pandemic infection and even after resolution. This occurs because
virus shedding peaks early, usually at onset of symp-
Human coronaviruses have classically caused mild toms, and continues for days or weeks following recov-
respiratory infections. Two previous outbreaks caused ery.4-6 The virus is an RNA (32KB genome) type, with a
by newly identified coronaviruses, SARS-CoV in 2002 rate of recombination up to 25%, and covered by a
and MERS-CoV in 2012, caused serious respiratory crown of glycoproteins that can also mutate fre-
disease with increased mortality. The current coronavi- quently.7,8 These characteristics may explain the adapt-
rus disease 2019 (COVID-19) pandemic is caused by ability of the virus and its infectivity changes over time.
SARS-CoV-2 (severe acute respiratory syndrome coro- The infection develops as the virus glycoprotein binds to
navirus 2).1,2 The infection originated late 2019 in ACE2 (angiotensin-converting enzyme 2) receptors that
China, and in a few months disseminated to reach are abundantly expressed in the lung.9 SARS viruses thus
almost 200 countries, now affecting over 500,000 peo- infect the cells of the pulmonary alveolus, causing acute
ple with an overall estimated mortality of 4% (World diffuse alveolar damage, edema, and inflammation,
Health Organization; March 27, 2020). which can evolve to acute respiratory distress syndrome
Rate of transmission of the virus is measured by the (ARDS) in adults.10 The disease is asymptomatic or
reproductive number (R0), which for SARS-CoV-2 is milder in children and young adults. Symptomatic adult
between 3.6 and 4 indicating high infectivity compared forms have increasing severity with age, although there
to influenza with R0 1.4 to 1.6.3,4 Importantly, transmis- have been notable exceptions to this age pattern, includ-
sion can occur during the presymptomatic phase of the ing in health care workers.11 Symptoms may develop
between 2 and 14 days after infection, with an average
-©- 2020
- - - - -International
- - - - - - - - - -Parkinson
- - - - - - - - and
- - - -Movement
- - - - - - - - Disorder
- - - - - - - -Society
------------ of 4 to 5 days, but cases of late onset of symptoms have
This article has been copublished in Movement Disorders and Move- been reported. COVID-19 can have a clinical presenta-
ment Disorders Clinical Practice tion similar to influenza, typically with fatigue, fever,
*Correspondence to: Dr. Stella M. Papa, Yerkes National Primate and nonproductive cough.12 Diarrhea has been the initial
Research Center, Department of Neurology, Emory University School
of Medicine, 201 Dowman Drive, Atlanta, GA 30322, USA;
symptom in fewer cases, indicating initial infection
E-mail: spapa@emory.edu through the gastrointestinal tract. Neurological symp-
Relevant conflicts of interest/financial disclosures: Nothing to toms can occur and include headache and nausea. In
report. addition, patients may report an intermittent or transient
Full financial disclosures and author roles may be found in the online loss of smell and taste. Most infected patients (approxi-
version of this article.
mately 80%) experience a mild clinical form and recover
Received: 31 March 2020; Accepted: 1 April 2020 without complications.13,14 However, among patients
Published online 00 Month 2020 in Wiley Online Library
with symptomatic forms, a proportion may require hos-
(wileyonlinelibrary.com). DOI: 10.1002/mds.28067 pitalization (30% in Europe, European Centre for
Movement Disorders, 2020 1P A P A E T A L
Disease Prevention and Control [ECDC] 3/25/2020), and, forms of coronaviruses in the cerebrospinal fluid of
of those, 50% (5% of the overall infected patients as patients with PD compared to other neurological dis-
tested) need intensive care because of pneumonia and eases and healthy controls.18
respiratory failure typically developing in 10 to 14 days, It is too early to know whether COVID-19 will have
requiring a prolonged duration of care (usually more than long-term neurological complications of exposure to
14 days; ECDC). Among the risk factors for presenting a SARS-CoV-2. The 1918 “Spanish” flu pandemic was
severe form, age is the most important with a progressive caused by influenza A (H1N1). A viral etiology of
rise starting at 50 years.11 Also, COVID-19 severity encephalitis lethargica and postencephalitic parkinson-
increases with comorbidities, particularly hypertension, ism, which followed temporally from the flu pandemic,
cardio- and cerebrovascular disease, diabetes, and immu- has been suspected although is still not proven, with
nosuppression.10,14 These comorbidities, together with some evidence implicating an enterovirus.19 Thus far,
age, are important prognostic factors. Antiviral drugs, coronaviruses have not been linked to specific long-
various antibodies, hydroxychloroquine, azithromycin, term neurological sequelae. Nonetheless, the observa-
ACE2 inhibitors, and other experimental agents, includ- tions of anosmia and ageusia are worthy of future
ing those aimed at mitigating the “cytokine storm” study. The facts that hyposmia is a common feature of
observed in severe cases, are among the COVID-19 treat- early PD (often even present in the prodrome) and that
ments currently under study, but thus far none is proven the olfactory system is an early predilection site for
or recommended for use outside of a controlled clinical alpha-synuclein pathology might just be an intriguing
setting. In addition, major research efforts are dedicated coincidence.20 However, it is notable that recent studies
internationally to developing an effective vaccine. indicate that alpha-synuclein participates in the innate
Several recent publications provide in-depth details to immune response to any viral infection, suggesting that
assess the impact of the COVID-19 pandemic on the these observations could be important.21
general population. In addition, it is hoped that it will
soon be possible to deploy antibody assays for wide- Is the PD Population Particularly
spread testing for immunity in large populations, all-
owing us to assess more accurately the dissemination of
Vulnerable During the COVID-19
the infection and mortality rate. Here, we will discuss Pandemic?
the significance of this viral infection with respect to the
central nervous system (CNS) and its relevance for It is too early to know whether COVID-19 will have
patients with Parkinson’s disease (PD) or other move- long-term impacts on patients with PD and movement dis-
ment disorders. orders. The increased vulnerability of the elderly and those
with comorbidities, coupled with the increased prevalence
of PD with age, raises concerns about the potentially height-
COVID-19 and Neurological ened risks of COVID-19 in people with PD and other
Manifestations movement disorders. In addition, the ability to provide stan-
dard neurological care is being compromised by the strain
From previous studies on SARS-CoV, we know that on health care systems brought about by this pandemic.
this virus infected the brain, including the brainstem, in There is currently insufficient evidence showing that
both patients and experimental animals.15 Following PD by itself increases the risk of COVID-19. The expe-
intranasal virus inoculation in mice, SARS-CoV or rience in Lombardia, Emilia, and Veneto, the three
MERS-CoV entered the CNS, possibly through the most affected regions in Italy, does not show an appar-
olfactory nerves, and, importantly, the viruses were ent increased risk, although there are no systematic
detected in the brain, but not in the lung, suggesting data available yet. A large population study22 found
direct transfer to the CNS by olfactory nerves.16 How- that in individuals aged ≥55 years, patients with PD
ever, detection of high viral load in the brainstem after had more physical and nonphysical comorbidities than
SARS-CoV infection is also indicative of infection patients without PD. In this study, there were 12 physi-
spreading to the CNS from the respiratory tract, which cal comorbidities significantly associated with PD,
is connected primarily by the vagus nerves to the including coronary artery disease, cerebrovascular dis-
ambiguus and solitary tract nuclei in the brainstem. ease, and heart failure, which are known to render
Involvement of this brain region may also suggest that patients at increased risk for more severe forms of
the cardiorespiratory center contributes to the severe COVID-19. In addition, both PD and more severe
respiratory distress caused by COVID-19.17 Importantly, forms of COVID-19, including higher mortality, show
the extent of SARS-CoV-2 invasion of the CNS, and its a clear preponderance of male sex.12-14
role in the respiratory distress and failure caused by the A retrospective cohort study conducted in Japan
infection, needs further investigation. A single study has showed that, compared to age- and sex-matched
reported enhanced antibody responses against different patients, patients with parkinsonism hospitalized for
2 Movement Disorders, 2020C O V I D - 1 9 P A N D E M I C A N D P D
pneumonia had a lower rate of in-hospital mortality, being moved and the evaluation of proposed projects
but a longer duration of hospitalization.23 The study postponed. Furthermore, it is difficult to predict how the
suggested that in-hospital mortality attributed to pneu- ongoing economic downturn will affect government
monia is not higher in parkinsonian patients, but it is and private sponsorship of research. Numerous confer-
not clear that this applies to those who have developed ences on PD and related disorders have already been
advanced ARDS. Furthermore, patients with PD pos- cancelled. On a positive note, there is also a flurry of
sess a higher risk of in-hospital complications, such as new activity using remote video conferencing to keep up
delirium, adverse drug reactions, syncope, aspiration the exchange of results and ideas in PD research during
pneumonia, falls, and fractures.24 Therefore, strategies the pandemic. Although it will take many months, or
to prevent these complications are essential. even years, before we can fully comprehend the impact
of the pandemic on laboratory research on PD, we
already know that it is and will remain significant.
A Special Role of Telemedicine Clinical research in PD is definitely highly impacted by
During the COVID-19 Pandemic the pandemic. Some jurisdictions or institutions have
prohibited the initiation of new clinical trials and
Patients with PD need routine visits to the hospital research. While this is understandable because of the
for physical assessment and medication adjustments by potential impact of COVID-19 on hospital resources
movement disorders specialists. However, hospital visits and out of concern for potential COVID-19 exposure to
should be avoided where possible during this period. trial patients during their visits, there are many unmet
Fortunately, the validity of telemedicine to assess PD clinical needs in people with PD and movement disor-
patients has been well documented in many studies, ders. Delays in clinical trials investigating potential
which is feasible because most physical examinations disease-modifying therapies in progressive neurodegener-
can be visualized.25 Indeed, many core features of the ative diseases, such as PD, or high-impact novel symp-
disease, except rigidity and postural reflex impairment, tomatic therapies should be minimized. In addition,
can be videotaped or watched with video consultations. consideration should be given to evaluating studies on a
The International Parkinson and Movement Disorder case-by-case basis rather than uniform suspensions of
Society has developed a practical step-by-step guide for research activity, which may cause a significant loss of
how to implement telemedicine for a movement disor- scientific and economic investment in clinical research.
ders clinic on their website, including the example of
providers and some regional specifics (https://www.
movementdisorders.org/MDS/About/Committees--Other-
Groups/Telemedicine-in-Your-Movement-Disorders-
Concluding Remarks
Practice-A-Step-by-Step-Guide.htm). Thus far, the comorbid diagnosis of PD itself or other
movement disorders has not emerged as a specific risk
Potential Medication Supply Issues factor for negative outcomes of COVID-19. The medi-
cal strategy for safety of patients with PD and the gen-
for PD Patients During the Pandemic eral elderly population is therefore not different and
The impact of the pandemic on global transport and based on advising social distancing and testing when-
supply chains, as well as manufacturing, has so far not ever necessary. Currently, we should rely on scientific
been reported to affect medication supply for patients proof and testing as many people as possible among
with PD. However, this situation needs to be monitored those involved in the care of our patients, followed
and communicated to clinicians in a timely manner so eventually by the necessary containment measures.
that they can work with their patients to make contin- Importantly, in any situation of unavoidable mea-
gency plans. sures of triage attributed to lack of intensive care
resources or ventilation equipment, there is no evidence
that patients with PD or any form of parkinsonism or
Disruption to Research and other movement disorders have less chance of survival
Clinical Trials from COVID-19 infection than patients with similar
age and comorbidities.
Numerous academic- and industry-based laboratories Finally, countries have to face the reality that individ-
investigating new therapies or diagnostics for PD have ual case containment might not be possible in the long
been forced to close or dramatically reduce their activi- term. As the health system moves from containment to
ties during the COVID-19 pandemic. Funding agencies mitigation, reintroduction of adequate management
are already discussing how to manage the situation and care of patients with PD, as well as resumption of
where projects are delayed, sometimes coupled to inevi- vital clinical and preclinical research, will be possible
table increases in cost. Grant submission deadlines are while still trying to control the COVID-19 outbreak
Movement Disorders, 2020 3P A P A E T A L
critically blunting its peaks.26 This global crisis, 3. Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of
SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020;20:
however, may significantly change the care for our 411–412.
patients with PD and other movement disorders toward 4. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper
better acceptance of telemedicine consultations and respiratory specimens of infected patients. N Engl J Med 2020;382:
assessments. 1177–1179.
5. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmis-
sion of COVID-19. JAMA 2020 Feb 21. https://doi.org/10.1001/
Recommendations and Priorities for Patients With jama.2020.2565. [Epub ahead of print].
PD and Movement Disorders 6. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan,
China, of novel coronavirus-infected pneumonia. N Engl J Med
• All measures of social distancing currently in 2020;382:1199–1207.
place for the general population almost globally 7. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the
must be strictly and carefully practiced. 2019-nCoV spike in the prefusion conformation. Science 2020;367:
1260–1263.
• Patients should avoid or postpone in-patient hos-
8. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associ-
pital stay for nonemergency reasons, given that ated with a new coronavirus of probable bat origin. Nature 2020;
hospitals can unfortunately be a source of further 579:270–273.
infection.27 9. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for
• Elective DBS surgeries may need to be postponed the recognition of the SARS-CoV-2 by full-length human ACE2. Sci-
ence 2020;367:1444–1448.
as well.
10. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical char-
• Outpatient visits can be substituted by the avail- acteristics of 99 cases of 2019 novel coronavirus pneumonia in
able tools of telemedicine and should only be per- Wuhan, China: a descriptive study. Lancet 2020;395:507–513.
formed when direct contact is necessary for 11. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mor-
adjusting or checking DBS programming, for DBS tality of adult inpatients with COVID-19 in Wuhan, China: a retro-
spective cohort study. Lancet 2020;395:1054–1062.
battery failure, or pump treatments.
12. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus
• Direct patient contact may be required for botuli- disease 2019 in China. N Engl J Med 2020 Feb 28. https://doi.org/
num toxin therapy on a carefully considered, as- 10.1056/NEJMoa2002032. [Epub ahead of print].
needed basis, ensuring adequate personal protec- 13. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospital-
ized patients with 2019 novel coronavirus-infected pneumonia in
tive equipment. Wuhan, China. JAMA 2020 Feb 7. https://doi.org/10.1001/jama.
• Quarantine may prevent patients with PD from 2020.1585. [Epub ahead of print].
an active lifestyle, which may already be impeded 14. Huang C, Wang Y, Li X, et al. Clinical features of patients infected
by pre-existing conditions, such as lack of motiva- with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:
497–506.
tion, physical disability, and mood problems. Vir-
15. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of
tual reality exercise games or home exercise SARS-CoV2 may play a role in the respiratory failure of COVID-19
instruments can be encouraged. patients. J Med Virol 2020 Feb 27. https://doi.org/10.1002/jmv.
• In case of COVID-19 infection, the physician 25728. [Epub ahead of print].
must ensure the maintenance of previous PD med- 16. Li K, Wohlford-Lenane C, Perlman S, et al. Middle East respiratory
syndrome coronavirus causes multiple organ damage and lethal dis-
ications, especially the adequate dosages of L- ease in mice transgenic for human dipeptidyl peptidase 4. J Infect
dopa/DDCI, as recommended for any type of Dis 2016;213:712–722.
pneumonia in parkinsonian patients to avoid 17. Matsuda K, Park CH, Sunden Y, et al. The vagus nerve is one route
of transneural invasion for intranasally inoculated influenza a virus
rigidity with contractures and respiratory impair- in mice. Vet Pathol 2004;41:101–107.
ment with reduced vital capacity and peak expira- 18. Fazzini E, Fleming J, Fahn S. Cerebrospinal fluid antibodies to coro-
tory flow.28 navirus in patients with Parkinson’s disease. Mov Disord 1992;7:
The International Parkinson and Movement Dis- 153–158.
order Society with this Viewpoint and other forth- 19. Dourmashkin RR, Dunn G, Castano V, McCall SA. Evidence for an
enterovirus as the cause of encephalitis lethargica. BMC Infect Dis
coming communications will endeavor to provide 2012;12:136.
updates and guidance for clinicians who care for PD 20. Rey NL, Wesson DW, Brundin P. The olfactory bulb as the entry
and movement disorder patients. site for prion-like propagation in neurodegenerative diseases. Neuro-
biol Dis 2018;109(Pt. B):226–248.
21. Tulisiak CT, Mercado G, Peelaerts W, Brundin L, Brundin P. Can
infections trigger alpha-synucleinopathies? Prog Mol Biol Transl Sci
2019;168:299–322.
22. McLean G, Hindle JV, Guthrie B, Mercer SW. Co-morbidity and
References polypharmacy in Parkinson’s disease: insights from a large Scottish
primary care database. BMC Neurol 2017;17:126.
1. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiol-
ogy of 2019 novel coronavirus: implications for virus origins and 23. Jo T, Yasunaga H, Michihata N, et al. Influence of Parkinsonism on
receptor binding. Lancet 2020;395:565–574. outcomes of elderly pneumonia patients. Parkinsonism Relat Disord
2018;54:25–29.
2. Coronaviridae Study Group of the International Committee on Tax-
onomy of viruses. The species Severe acute respiratory syndrome- 24. Lubomski M, Rushworth RL, Tisch S. Hospitalisation and com-
related coronavirus: classifying 2019-nCoV and naming it SARS- orbidities in Parkinson’s disease: a large Australian retrospective
CoV-2. Nat Microbiol 2020;5:536–544. study. J Neurol Neurosurg Psychiatry 2015;86:324–330.
4 Movement Disorders, 2020C O V I D - 1 9 P A N D E M I C A N D P D
25. Ben-Pazi H, Browne P, Chan P, et al. The promise of telemedicine 27. Nacoti M, Ciocca A, Giupponi A, et al. At the epicenter of the
for movement disorders: an interdisciplinary approach. Curr Neurol COVID-19 pandemic and humanitarian crises in Italy: changing per-
Neurosci Rep 2018;18:26. spectives on preparation and mitigation. NEJM Catalyst 2020 Mar
26. Wilder-Smith A, Chiew CJ, Lee VJ. Can we contain the COVID-19 21. https://doi.org/10.1056/CAT.20.0080. [Epub ahead of print].
outbreak with the same measures as for SARS? Lancet Infect Dis 28. Monteiro L, Souza-Machado A, Valderramas S, Melo A. The effect
2020 Mar 5. pii: S1473-3099(20)30129-8. https://doi.org/10.1016/ of levodopa on pulmonary function in Parkinson’s disease: a system-
S1473-3099(20)30129-8. [Epub ahead of print]. atic review and meta-analysis. Clin Ther 2012;34:1049–1055.
Movement Disorders, 2020 5SGML and CITI Use Only
DO NOT PRINT
Author Roles
Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
Stella M. Papa: A, B
Patrik Brundin: A, B
Victor S.C. Fung: A, B
Un Jung Kang: A, B
David J. Burn: A, B
Carlo Colosimo: A, B
Han-Lin Chiang: A, B
Roy N. Alcalay: A, B
Claudia Trenkwalder: A, B
Financial Disclosures
Dr. Papa has received research support from NIH-NINDS (NS45962, NS073994, NS110416, NCRR RR000165,
and ORIP/OD OD011132), Forum Pharmaceuticals, Inc., Mochida Pharmaceuticals Co. LTD, and Circuit Therapeu-
tics, Inc. She has been a consultant for Mochida Pharmaceuticals Co. LTD and Teva Neuroscience. Dr. Patrik
Brundin has received commercial support as a consultant from Axial Biotherapeutics, CuraSen, Fujifilm-Cellular
Dynamics International, IOS Press Partners, Lundbeck A/S, and Living Cell Technologies LTD. He has received com-
mercial support for research from Lundbeck A/S and Roche. He has ownership interests in Acousort AB and Axial
Biotherapeutics and is on the steering committee of the NILO-PD trial. Dr. Fung receives a salary from NSW Health;
has received unrestricted research grants from the Michael J. Fox Foundation, AbbVie, and Merz; is on advisory
boards for and/or has received travel grants from AbbVie, Allergan, Cavion, Ipsen, Merz, Praxis, Seqirus, Stada,
Teva, and UCB; and receives royalties from Health Press Ltd. Dr. Colosimo has received grants and honoraria from
AbbVie, Alfasigma, BIAL, Ipsen, and Zambon and royalties from Oxford University Press and Cambridge University
Press. Dr. Alcalay has received consultation fees from Janssen and Sanofi.You can also read
